The Laboratory of Molecular Bases of Pathogenesis

e-mail:
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Lab members:

Leading researcher:

1. Chernova Olga A., D.Sc. (Biochemistry), professor,
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Senior researchers:

2. Davydova Marina N., Cand.Sc.,
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3. Ryazantseva Irina N., Cand.Sc.,
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Researchers:

4. Shaymardanova Gulnara F., Cand.Sc.,
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5. Trushin Maxim V., Cand.Sc.,
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6. Nesterova Tatyana N., Cand.Sc.,
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Junior researchers:

7. Mouzykantov Alexey A., Cand.Sc.,
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8. Baranova Natalia B., Cand.Sc.,
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9. Medvedeva Elena S., Cand.Sc.,
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Postgraduate student:

10. Grigoryeva Tatyana
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Historical Background

In June 1987, a Group of Molecular Genetics of Plant Mycoplasmas was established at the Institute owing to the initiative of academician I.A. Tarchevsky; in June 1988, this Group was transformed into the Laboratory of Molecular Genetics of Mycoplasmas. The Declaration of the Central Committee of Communist Party of the Soviet Union and the USSR Cabinet of Ministry of August 26, 1985 (#807) – “On further development of new directions in biology and biotechnology” formed the basis for the foundation of a new Laboratory and initiation of research of the molecular-genetic fundamentals of interaction between plants and pathogenic microorganisms within the Institute.

The choice of mycoplasmas as a model of pathogenic microorganisms was defined by the unicity of organization of the smallest prokaryotes the limited biosynthetic abilities of which did not prevent their broad distribution in the nature, overcoming the defense systems of higher eukaryotes and persistence. Much attention to mycoplasmas is given because of the practical necessity: mycoplasmas are parasites of humans, animals, plants, and main contaminants of cell cultures widely used in biotechnology. Control of mycoplasma infections and contaminations presents a serious problem the resolution of which is connected with the advantages of investigation of interaction between mycoplasmas and higher eukaryotes, and adaptation of these microorganisms to stressors.

The first researchers of the Laboratory were V.M. Chernov and O.A. Chernova (post-graduate students of the Institute of Cytology, USSR Academy of Sciences, Leningrad), M.A. Khasanova (post-graduate student of the Institute of Biochemistry and Physiology of Microorganisms, USSR Academy of Sciences, Puschino-na-Oke) and an engineer Yu.V. Gogolev (from the Laboratory of Biochemistry of Cell Wall under Prof. V.V. Lozovaya).

In 2002 the Laboratory was renamed as the Laboratory of Molecular Fundamentals of Pathogenesis. In 2003, a group of microbiologists headed by Dr. M.N. Davydova was incorporated into the Laboratory. Previously, the scientific workers of the group formed the main part of the Laboratory of Physiology and Biochemistry of Anaerobic Bacteria, founded in 1976 by an eminent professor M.I. Belyaeva. In 2006, a part of the researchers joined a Group of Molecular Biology headed by Dr. Yu.V. Gogolev.

Much of the scientific work of the Laboratory is related to the investigation of molecular and cell biology of mycoplasmas that infect humans, animals, plants, the main contaminants of cell cultures and vaccines.

The success of the genome projects for mycoplasmas determined the feasibility of comparative proteomic profiling of these microorganisms cultivated under stress conditions as well as of higher organisms with mycoplasmas.Studies on the genome-transcriptome-proteome analysis of mycoplasmas and eukaryotesare supplemented with the investigations of the ultrastructure of cells interacting organisms.

The basic research topic of the Laboratory is the interaction between mycoplasmas and eukaryotes: the analysis of genomes’, proteomes’, transcriptoms’.

Basic results for 2007-2012:

Members of the Laboratory for the first time performed the data of proteomic and transcriptomic analysis of mycoplasma cells cultured under different environments, as well of eukaryotes, infected with mycoplasma. As a result of these investigations, proteins and genes mediating mycoplasma response reactions to stressors, as well as those in eukaryotes after mycoplasma infection were identified.

It was revealed for the first time that adaptation of mycoplasmas to stress conditions was connected with intensification of the process of releasing from bacterial cells membrane vesicles -spherical membrane-bound nanostructures (diameter 20-120 nm). It was demonstrated that membrane vesicles of mycoplasmas, apart from lipids and proteins, also included genetic material and were active participants in pathogenesis. With the use of atomic force microscopy, 3D images of mycoplasma cells and secreted membrane vesicles were obtained.

Applied research:

The investigations on technologic application of bacterial pigments in polymer coloring in chemical industry conducted as a result, the method for utilization of bacterial pigments in technology of polyoleofine coloring has been developed and patented. Synthesis of microbial pigments was performed using intermediates of cell metabolism. It excludes expenses for multistage synthesis of pigment molecule and is recognized as the ecologically pure process.

Work on personnel training:

Under the guidance of the Laboratory staff for 2003-2012, the following Cand.Sc. dissertations were defended:

Russian Fund for Basic Research 98-04-48972a. Genetic variation in mycoplasmas during their interaction with eukaryotes: the variable genome cites and ways of its re-organization.

Russian Fund for Basic Research 01-04-49885a. Transformation of nitric ether of cellulose by sulfate-reducing bacterium.

Russian Fund for Basic Research 01-04-49011a. Interaction of plants with mycoplasmas: cellular and molecular features of plant response to infection and persistence of the parasite.

Russian Fund for Basic Research 01-04-49008a. Polymorphism of mycoplasmas in populations of Volga region: the feaures of ultracytostructure and variability of genes of cytoadhesines of clinical isolates.

Russian Fund for Basic Research 08-04-01047a. Molecular basis of mycoplasma adaptation (M. gallisepticum) to biogenic and abiogenic stressors: proteins of nanoforms and their genes. 2008-2010.

Russian Fund for Basic Research 11-04-01406а. Molecular fundamentals of mycoplasma adaptation to biotic and abiotic stressors: proteins of membrane vesicles secreted by cells of Acholeplasma laidlawii PG8, and their genes. 2011-2013.

Russian Fund for Basic Research 12-04-31396.Formation mechanisms of resistance to antibiotics of mycoplasma: secretion of extracellular membrane vesicles and efflux of ciprofloxacin in Acholeplasma laidlawii PG8. 2012-2013.

Russian Fund for Basic Research 12-04-01052a. Phytopathogenicity and secretory system of mycoplasmas: virulence factors are exported through the membrane vesicles. 2012-2014.

NIOKR-Tatarstan 03.3.10-163/2002-2004 (F). “Polymorphism of microorganisms associated with diseases of gastrointestinal tract in human populations of Republic of Tatarstan: features of ultracytostructure and genetic variability of Helicobacter pylori clinical isolates and mycoplasmas”.

NIOKR-Tatarstan 03.3.10-361/2005 (F). ‘Genetic polymorphism in human populations of Republic of Tatarstan: variability of genes of cytokines in patients with gastro-duodenal and urogenital diseases at helicobacter and mycoplasma infections”.

Grant by the President of Russian Federation to young scientists № МК-3372.2009.4.

Grant by the President of Russian Federation to young scientists № МК-4894.2010.4.

Grant by the President of Russian Federation to young scientists № МК-3823.2013.4.

Federal Purposive Program “Investigation and developments for science and technique for 2002-2006”. Government contract # 02.442.11.7283 (Principal investigator – Prof. Chernov) “Molecular and genetic mechanisms of mycoplasma adaptation to biogenic and abiogenic stressors”.

Federal Purposive Program ‘Living systems”. Government contract # 02.512.11.2067 (Principal investigator – Prof. Chernov) “Comparative proteome analysis of vegetative forms and nanocells of M. gallisepticum for development of technology for control of mycoplasma infections”.

Federal Purposive Programm ‘Living systems”. Government contract # 02.512.12.2010 (Principal investigator – Prof. Chernov): “Proteome-transcriptome analysis of mycoplasma cells and eukaryotes during their interaction for development of methods for control of the parasite-host system”. 2008-2009.

Program of the Presidium of RAS «Support of innovations». «Potential of secondary metabolites of microorganisms for practical application». 2008.

Federal Purposive Program «Scientific and scientific-educational personnel of the innovation Russia» for 2009-2013 on the lot «Performing of scientific research by collectives of scientific-educational centers in the area of technical sciences» – Governmental contract № 02.740.11.0391 «Secreted factors of toxigenicity of bacteria as promising tools for control of pathogenic processes». 2009-2011.

Federal Purposive Program «Scientific and scientific-educational personnel of the innovation Russia» for 2009-2013. Agreement of 20 July 2012 #8042 “Investigation of new class of secreted bacterial toxigens – extracellular membrane vesicles of mycoplasmas for development of ways for controlling mycoplasma infections, contamination of cell cultures and vaccines”. 2012-2013.